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Genes that respond to fatty diet may portend obesity
By Roberta Friedman

Obesity researchers have identified genes that are turned on by fats floating in the bloodstream after a meal. In rodents, the pattern of gene expression is influenced by an animal's propensity to store and maintain excess fat garnered from food, according to findings presented last week at the meeting of the American Association for the Advancement of Science in San Francisco.

The genes that respond are stimulated by fat in the diet, and they also react to elevated body fat. They code for small proteins, or peptides, involved in the brain's messaging system that creates appetite, and for peptide carriers of molecules that regulate where in the body fat is deposited.

One gene codes for apolipoprotein D, and is over-expressed in the brains of animals on a high fat diet, says Sarah Leibowitz, of The Rockefeller University in New York. Leibowitz uses a technique called quantitative optic PCR to identify differences in gene expression in response to fat intake. The method can detect changes in gene expression of 20 to 50 percent. "These techniques are allowing us to broaden our understanding" of how people become fat, says Leibowitz. Apolipoprotein D "may help process the lipids that impact on the brain and control gene expression."

Leibowitz is screening for genes in the hypothalamus that are expressed differently in animals prone to obesity compared to those that remain lean despite a diet of fatty food.

A single high-fat meal is sufficient to stimulate the fat-responsive genes in the region of the brain already linked to the control of body weight, the hypothalamus. Leibowitz is collecting evidence that there are overactive genes in the hypothalamus even in young adults whose body weight is in the normal range but who are at risk for obesity if given a high-fat diet.

"The obesity-prone animals invariably have higher levels of the fat-promoting peptides," Leibowitz says. "Already the stage is set for the problem" by peptides involved in the fat-regulating circuitry of the brain and endocrine system, such as galanin and orexin. These peptides can 'overrule' leptin, a mediator that signals satiety; "They don't listen" to the leptin message that enough food has been consumed, Leibowitz says. Her findings will be published in the Journal of Biological Chemistry in the coming months, she says.

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